Porth's Essentials of Pathophysiology, 4e

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Disorders of Gastrointestinal Function

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TABLE 29-1 Differentiating Characteristics of Crohn Disease and Ulcerative Colitis Characteristic Crohn Disease

Ulcerative Colitis

Types of inflammation Level of involvement Extent of involvement Areas of involvement

Granulomatous

Ulcerative and exudative

Primarily submucosal

Primarily mucosal

Skip lesions

Continuous

Primarily ileum, secondarily colon

Primarily rectum and left colon

Diarrhea

Common

Common Common

Rectal bleeding

Rare

Fistulas

Common Common Common

Rare Rare Rare

Strictures

Perianal abscesses

Development of cancer

Uncommon

Relatively common

duct (i.e., sclerosing cholangitis). Occasionally, these systemic manifestations may herald the recurrence of intestinal disease. In children, growth retardation may occur, particularly if the symptoms are prolonged and nutrient intake has been poor. Etiology and Pathogenesis The causes of Crohn disease and ulcerative colitis are largely uncertain. There is growing evidence that the two diseases result from a combination of intestinal microor- ganisms, intestinal epithelial dysfunction, and aberrant immune responses in a genetically predisposed host. 6 The genetic basis for IBD has long been suspected. The risk of disease is greater when there is an affected family member, with a family history of IBD being more common in Crohn disease than ulcerative colitis. 6,7,27 Molecular linkage analyses of affected families have identified NOD2 (nucleotide oligomerization domain 2) as a susceptibility gene in Crohn disease. 6,27,29 The NOD2 gene encodes a protein that is an intracellular recep- tor for a component of the cell wall of many microbes and is thought to play a role in host responses to these pathogens. It has been postulated that disease-associated NOD2 is less effective in recognizing and eliminating luminal microbes. 6,27,28 The fact that fewer than 10% of individuals carrying the NOD2 mutations develop Crohn disease suggests that it is only one of many fac- tors that contribute to the pathogenesis of the disease. The intestinal microbiome consists of the microorgan- isms that inhabit the gut. 6,27 These organisms play a key role in development of the intestinal immune system and supplying the body with key nutrients such as vitamin B 12 . Although acquired shortly after birth, each person’s microbiome changes rapidly during the first year of life. Moreover, although each adult has a unique popula- tion of microbiota that remains fairly stable over time, changes occur in response to environmental and develop- mental factors, and disease. Despite the growing evidence that intestinal microorganisms contribute to IBD patho- genesis, their precise role remains to be described and is probably different in Crohn disease and ulcerative colitis. A variety of epithelial defects have been described in both Crohn disease and ulcerative colitis. 6,27 The intes- tinal epithelium at the interface between the intestinal microbiome and the wall of the gastrointestinal tract

plays a critical role in preventing the entry of bacteria and shaping the mucosal immune response. An intact mucosal barrier depends on tight epithelial cell junc- tions that help to seal the space between the intesti- nal contents and the underlying tissues of the intestinal wall. Additional defenses against bacterial invasion con- sist of specialized epithelial cells, including the goblet cells, which regulate production of mucus and factors that contribute to epithelial repair and regulation of inflammation, and the Paneth cells, which secrete anti- microbial peptides (see Chapter 28, Fig. 28-11). A variety of other factors are associated with IBD for unknown reasons. 6,7 For example, an episode of appen- dicitis is associated with a decreased risk of developing ulcerative colitis. Also, smoking tobacco has opposite effects on the two forms of inflammatory bowel disease. It predisposes to development of Crohn disease, yet is associated with a reduced incidence of ulcerative colitis. Crohn Disease Crohn disease is a recurrent, granulomatous type of inflammatory response that can affect any area of the gastrointestinal tract. In half the cases, the disease affects mainly the ileum and cecum, only the small intestine in 15%, only the colon in 20%, and mainly the anorec- tal region in 15%. 7 It is a slowly progressive, relentless, and often disabling disease. The disease usually strikes people in their twenties or thirties, with women being affected slightly more often than men. Clinical Manifestations. A characteristic feature of Crohn disease is the sharply demarcated, granuloma- tous lesions that are surrounded by normal-appearing mucosal tissue. When the lesions are multiple, they often are referred to as skip lesions because they are inter- spersed between what appear to be normal segments of the bowel. All the layers of the bowel are involved, with the submucosal layer affected to the greatest extent. The surface of the inflamed bowel usually has a character- istic “cobblestone” appearance resulting from the fis- sures and crevices that develop, surrounded by areas of submucosal edema 6,7 (Fig. 29-6). There usually is a rela- tive sparing of the smooth muscle layers of the bowel, with marked inflammatory and fibrotic changes of the submucosal layer. After a time, the bowel wall often becomes thickened and inflexible; its appearance has